1. Field of the Invention
The present invention relates to a selective process for the preparation of basic coumarin derivatives (I) and of their salts formed by the reaction with organic and inorganic salts. In the formula I ##STR1## R.sub.1 is selected from alkyl groups having thereon basic substituents, such as piperidino ethyl, morpholino ethyl, diethylamino ethyl or diethylamino propyl; R.sub.2 is selected from the group consisting of hydrogen, alkyl and aryl; R.sub.3 is selected from the group of alkyl radicals substituted with a basic group, an alkenyl group, a carboxy alkyl group or an alkoxy carbonyl alkyl group; and wherein X represents a halogen atom in the 8 position.
The process according to the invention makes it possible to obtain as final products monohalogenated derivatives of 7-hydroxycoumarin of the formula: ##STR2## which, by virtue of the selective process which forms the object of the present invention, give the certainty that the halogen atoms are in position 8; said final products, as it will be shown hereafter, are thus obtained in grade and purity sufficient to exercise a vasodilatory action effectively, in particular with respect to coronary vessels in animals and humans.
2. Prior Art
It is already known a pharmaceutical product under the generic name of `carbochromene` of the general formula: ##STR3##
There are also patented (see U.S. Pat. No. 3,515,721) some mono- and di-halogen derivatives obtained according to the scheme described in the cited patent and having the general formula: ##STR4##
Said compounds also possess specific coronary vasodilatory activity but to a lower degree (see compound No. 4 and 10 in the attached table), according to data furnished in the said patent, with respect to carbochromene (compound No. 2 of the table).
Furthermore, in said patent, it is stated that there is obtained in the case of monohalogenated derivatives a single final product and only in the corresponding British specification No. 1,146,792 it is specified that the halogen is in position 8.
Such product is in fact composed of a mixture of derivatives of 7-hydroxy-coumarin and there are also present therein compounds having a halogen atom in the position indicated by X: position 8 or position 6.
The uncertainty on where the halogen is located is due to the procedure followed by the patent; since the halogen is introduced during an intermediate phase of the process, it is not possible to determine with certainty what position will the halogen occupy.